The microstructural type of trabeculae (plate-like vs. rod-like) is critical in determining the strength of trabecular bone while a dramatic change of trabeculae from plate-like to rod-like occurs in aging and osteoporosis. This Bioengineering Research Grant is to develop a novel morphological and micro-mechanical modeling method based on digital topological analysis (DTA) of muCT and muMRI images of trabecular bone with the following specific aims: Specific Aim 1: To perform muCT and muMRI imaging on trabecular bone specimens from human cadaveric vertebrae, proximal tibiae, and proximal femurs, and to perform uniaxial compression tests to experimentally determine mechanical properties of human trabecular bone. Specific Aim 2: To perform non-linear voxel based muFE analyses on muCT and muMRI images and DTA based segmentations for individual trabeculae to quantify micromechanics of trabecular bone failure. Specific Aim 3: To perform DTA based morphological analyses on muCT and muMRI images and correlate new morphological parameters to experimentally determined mechanical properties of human trabecular bone. Specific Aim 4: To develop reduced plate/rod muFE models based on DTA segmentation of both muCT and muMRI images and to compare nonlinear predictions of reduced plate/rod models with those of voxel based models;To perform nonlinear muFE analyses of whole vertebral bodies using reduced muFE models and to compare nonlinear predictions of reduced models with those of voxel based models to be performed at UC Berkeley (supported NTH project). In the process of performing the above specific aims, we will test the following hypotheses: Hypothesis 1: Independent of anatomic sites, yielding is initiated in trabecular rods and then is equally distributed in both trabecular plates and rods at later stages in trabecular bone failure. Hypothesis 2: Mechanical properties of trabecular bone can be predicted by morphological parameters based on DTA segmentation of individual trabecular rods/plates. Hypothesis 3: The predictions of mechanical properties and micromechanics of trabecular bone are independent of imaging modalities (muCT vs. muMRI) and model types (voxel vs. reduced plate/rod). New morphological and micromechanical modeling tools of trabecular bone microstructure will be developed for studying failure mechanisms and fracture risk assessment for a whole human bone at an individual trabecula level.